The structural lability of the largest virion polypeptide (VPI) of type 1 poliovaccine has been used to identify mutations occurring in virus strains isolated from human feces. Following vaccine feeding, a mutant of the vaccine is progressively selected after several replication cycles in the gut. This mutant, which has altered antigenic properties and has regained the capacity to synthesize a stable VPI, may be responsible for rare instances of vaccine-associated paralytic disease.